Embryonic stem cells are promising candidates for a source of cells for cell transplantation for Parkinson's disease and diabetes mellitus. However, even embryonic stem cells derived from mice, humans and other primates require the coexistence with mouse-derived feeder cells (stromal cells) in their culture and differentiation induction, and this represents a major barrier against their clinical applications.
Recently, the present inventors developed a method of inducing the differentiation of mouse and monkey embryonic stem cells into neurons at high efficiency (SDIA method) (see pamphlet for International Patent Publication No. WO01/088100; pamphlet for International Patent Publication No. WO03/042384; Kawasaki et al., Neuron, vol. 28, p. 31-40 (2000); Kawasaki et al., Proceedings of the National Academy of Sciences of the USA, vol. 99, p. 1580-1585 (2002); Mizuseki et al., Proceedings of the National Academy of Sciences of the United States of America, vol. 100, p. 5828-5833 (2003); Ooto et al., Invest. Opthalmol. Vis. Sci., vol. 44, p. 2689-2693 (2003)). Using this method, the present inventors succeeded in producing in vitro dopamine-secreting neurons, which are expected to be applied to transplantation therapy for Parkinson's disease, and motor neurons, which are speculated to be applied to treatment for amyotrophic lateral sclerosis, from mouse and monkey embryonic stem cells (see pamphlet for International Patent Publication No. WO01/088100; pamphlet for International Patent Publication No. WO03/042384; Kawasaki et al., Neuron, vol. 28, p. 31-40 (2000); Kawasaki et al., Proceedings of the National Academy of Sciences of the USA, vol. 99, p. 1580-1585 (2002); Mizuseki et al., Proceedings of the National Academy of Sciences of the United States of America, vol. 100, p. 5828-5833 (2003); Ooto et al., Invest. Opthalmol. Vis. Sci., vol. 44, p. 2689-2693 (2003)). Also, as another method of inducing the differentiation of neurons from embryonic stem cells, the multistep differentiation method is known (see Lee et al., Nature Biotech., vol. 18, p. 675-679 (2000)).
However, by the SDIA method and the multistep differentiation method, midbrain tissues such as dopamine nerves could be differentiation-induced efficiently, but forebrain tissues such as telencephalic tissue could only been induced at low efficiency.
Against this background, there has been a strong demand for the development of a method enabling the efficient induction of differentiation of embryonic stem cells into a forebrain tissue such as telencephalic tissue.